Dysfunctions of the basal ganglia have been implicated in extrapyramidal movement disorders such as Parkinson's disease and Huntington's disease, and the basal ganglia are abnormal in some neuropsyctuatric disorders as well. No clear idea has yet emerged, however, about what neural operations are performed in the basal ganglia. Strong evidence suggests that the functions of the basal ganglia must depend heavily on their cortical inputs, because the neocortex provides most of the inputs that the basal ganglia receive. These inputs enter mainly by way of corticostriatal projections to the striatum, and indirectly via the thalamus. The largest outputs of the basal ganglia in turn link these nuclei, through series of synaptic steps, to the motor, promotor and prefrontal cortex. The basal ganglia thus appear. to receive cortical input, process it under the influence of modulatory inputs (for example dopaminergic) and return it to the frontal lobes (and to some brainstem sites). We propose a coordinated series of experiments in monkeys and rats to study cortical-based ganglia linkages. Specifically, we propose to analyze in detail the sensorimotor cortical projections to the striatum. This sensorimotor system has significant advantages for study: the inputs are strong, they can be identified electrophysiologically by recording and microstimulation in the cortex, they can be mapped rigorously with sensitive tracer methods, and they thus can be analyzed in depth to permit stud of the map-transformations that occur between cortex and striatum. Much of the proposed work on this system (AIMS 1,2 and 4) is to be in squirrel monkey, in which we and others have found a distributed, catchy organization of inputs from primary somatosensory and motor cortex to the putamen. We will attempt to determine the rules of organization of these distributed and modular sensorimotor inputs. A series of studies is also proposed in the rat to attempt delineation of striatal cells activated by the sensorimotor cortex. In these experiments we propose (in AIM 3, with follow-up in the squirrel monkey in AIM 4) to use electrical and chemical stimulation of sensorimotor cortex to activate immediatearly genes in striatal neurons. The gene expression will be used as a cellular-level readout of neural ensembles activated by cortical input in the striatum and its output targets, and the pathways necessary for this activation will be determined. With these two complimentary techniques, our goal is to delineate the organization of corticostriatal sensorimotor maps in sufficient detail to gain insight into the functions of the striatum. The significance of this work is twofold. First, it may help uncover the neural substrates of focal and somatotypically distributed banal ganglia movement disorders. Second, it should help identifying what transformations occur in cortical-basal ganglia loops.
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